Paeonol Attenuated Vascular Fibrosis Through Regulating Treg/Th17 Balance in a Gut Microbiota-Dependent Manner

Background: Paeonol (Pae) is a natural phenolic compound isolated from Cortex Moutan, which exhibits anti-atherosclerosis (AS) effects. Our previous work demonstrated that gut microbiota plays an important role during AS treatment as it affects the efficacy of Pae. However, the mechanism of Pae in protecting against vascular fibrosis as related to gut microbiota has yet to be elucidated.Objective: To investigate the antifibrosis effect of Pae on AS mice and demonstrate the underlying gut microbiota-dependent mechanism.Methods: ApoE-/- mice were fed with high-fat diet (HFD) to replicate the AS model. H&E and Masson staining were used to observe the plaque formation and collagen deposition. Short-chain fatty acid (SCFA) production was analyzed through LC-MS/MS. The frequency of immune cells in spleen was phenotyped by flow cytometry. The mRNA expression of aortic inflammatory cytokines was detected by qRT-PCR. The protein expression of LOX and fibrosis-related indicators were examined by western blot.Results: Pae restricted the development of AS and collagen deposition. Notably, the antifibrosis effect of Pae was achieved by regulating the gut microbiota. LC-MS/MS data indicated that the level of SCFAs was increased in caecum contents. Additionally, Pae administration selectively upregulated the frequency of regulatory T (Treg) cells as well as downregulated the ratio of T helper type 17 (Th17) cells in the spleen of AS mice, improving the Treg/Th17 balance. In addition, as expected, Pae intervention can significantly downregulate the levels of proinflammatory cytokines IL-1β, IL-6, TNF-α, and IL-17 in the aorta, and upregulate the levels of anti-inflammatory factor IL-10, a marker of Treg cells. Finally, Pae’s intervention in the gut microbiota resulted in the restoration of the balance of Treg/Th17, which indirectly downregulated the protein expression level of LOX and fibrosis-related indicators (MMP-2/9 and collagen I/III).Conclusion: Pae attenuated vascular fibrosis in a gut microbiota-dependent manner. The underlying protective mechanism was associated with the improved Treg/Th17 balance in spleen mediated through the increased microbiota-derived SCFA production. Collectively, our results demonstrated the role of Pae as a potential gut microbiota modulator to prevent and treat AS.

Insight into Seasonal Change of Phytochemicals, Antioxidant, and Anti-Aging Activities of Root Bark of Paeonia suffruticosa (Cortex Moutan) Combined with Multivariate Statistical Analysis

Chemical compositions, antioxidants, and anti-aging activities of Cortex Moutan (CM), from different collection periods and different producing areas, were measured and compared in order to obtain excellent CM extracts. The bioactivities of CM extracts were examined by an in vitro antioxidant method and a UVB irradiated human dermal fibroblast (HDF) model. Phytochemical properties were obtained from ultra-fast liquid chromatography quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF-MS) prior to the multivariate statistical analysis. As for the results, the extracts of Heze CM (HZCM) and Luoyang CM (LYCM) collected in June had better in vitro antioxidant activities, significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reduced the content of malondialdehyde (MDA), compared to other CM extracts. HZCM and LYCM extracts could upregulate the relative expression of SOD and GSH-Px mRNA. The extract of HZCM collected in June could significantly repress the production of matrix metalloproteinase 1 (MMP-1) and improve the production of procollagen type I (PCOL)-I in UVB irradiated HDF. In total, 50 compounds, including 17 monoterpenoids, 19 flavonoids, 13 phenols, and 1 amino acid were identified or tentatively identified in the CM extracts. Gallic acid, p-hydroxybenzoic acid, oxypaeoniflorin, paeoniflorin, 1,2,3,4,6-O-pentagalloyl glucose, and paeonol were predominant compounds in the CM extracts. Taken together, CM collected from April to September had better antioxidant and anti-aging effects for external usage.

Plant Extracts in Obesity: A Role of Gut Microbiota

Obesity has become one of the most serious chronic diseases threatening human health. Its occurrence and development are closely associated with gut microbiota since the disorders of gut microbiota can promote endotoxin production and induce inflammatory response. Recently, numerous plant extracts have been proven to mitigate lipid dysmetabolism and obesity syndrome by regulating the abundance and composition of gut microbiota. In this review, we summarize the potential roles of different plant extracts including mulberry leaf extract, policosanol, cortex moutan, green tea, honokiol, and capsaicin in regulating obesity via gut microbiota. Based on the current findings, plant extracts may be promising agents for the prevention and treatment of obesity and its related metabolic diseases, and the mechanisms might be associated with gut microbiota.

A MECHANISTIC INSIGHT OF NATURAL PRODUCTS FOR ECZEMA TREATMENT (PART I)

Eczema is termed as a chronic relapsing atopic dermatitis which is a chronic, inflammatory dermatosis mediated by immune system and is characterized by T- helper 2 immune response phenotype. Eczema is associated with disturbance in sleep and it also affects the quality of life. Emollient, antimicrobial agents, corticosteroid or immune-modulating agents are used for treatment of eczema. Pathogenesis of eczema involves complex interactions between susceptible genes, immunological factor, and defects in skin barriers, neuro-endocrine factors and factors related to environment like change in weather, food and aeroallergens. Because there is no cure till date for eczema, Chinese medicines which are part of dietary therapies are being adopted by the Asian patients. In the treatment of skin disorders and wounds a tremendous role has been played by Herbal extracts and isolated plant compounds. Recently a lot of new herbal drugs have been developed that were tested in controlled clinical or preclinical studies. St. John’s wort, licorice, tormentil, bitter substances, evening primrose and many more biomedicines, topical agents: coconut oil, colloidal oatmeal, sunflower oil, mustard oil, glycerin, and oral Chinese herbal therapy are used to treat AD. Probiotics, and vitamins are also used as oral agents in treatment of AD and all these bioagents have shown good results in treatment of atopic dermatitis. Wind, dampness and heat are the three main pathogenic factors of eczema. Various Chinese herb such as cortex moutan radix (danpi), radix paeoniae alba (bai shao), potentilla chinensis ser (weilingcai) and radix glycyrrhizae (gan cao) are common treatments for eczema allergy. It is being indicated in pharmacological studies that these herbs have anti-allergic, anti- inflammatory and sedative action for itchiness . These studied medicinal plants were found to be effective in eczema therapy, further mechanistic and clinical studies are required to establish this claim.

Study on traditional Chinese medicine medication for acne of wind-heat type in lung meridian based on data mining and network pharmacology

Acne vulgaris of wind-heat in lung meridian is a common skin disease, and there are many traditional Chinese medicine prescriptions, but the mechanism is still not clear. In this paper, the literature on the treatment of acne due to wind-heat in lung meridian and the prescriptions in the patents were collected and sorted out in the past twenty years. Excel 2019 was used for medication frequency statistics, and IBM SPSS 25.0 was used for clustering analysis to obtain the core formula. Network pharmacology was used to collect the related targets of drugs and diseases, to construct the action network, and to conduct enrichment analysis. A total of 137 prescriptions and 167 drugs were obtained. The core prescriptions were Cortex mori, Folium eriobotryae, Scutellariae radix, Glycyrrhrizae radix, Fructus gardeniae, Radix rehmanniae, and Cortex moutan. The treatment of acne due to wind-heat in lung meridian should begin with clearing heat, purging the lung, cooling blood and detoxicating. The core prescriptions mainly played a role through AKT1, IL6, TP53, TNF, VEGFA, EGF targets and Kaposi's sarcoma-related herpes virus infection, measles, toxoplasmosis, EB virus infection, IL-17, MAPK and other signaling pathways, so as to provide reference for further clinical research.

Chemical Fingerprinting and Quantitative Analysis of Cortex Moutan From Different Tree Peony Cultivars Using HPLC-ESI/MS

To evaluate the relationship between tree peony cultivars and the quality consistency of Cortex Moutan, a sensitive, reliable, and validated method based on high-performance liquid chromatography-electrospray ionization/mass spectrometry was developed for the quantitative analysis of paeonol and chemical fingerprinting of Cortex Moutan. Results from quantitative analysis showed that the content of paeonol in Paeonia ostii “Feng Dan” was the highest (24.51 ± 0.83 mg/g), followed by Paeonia suffruticosa “Luoyang Hong” (14.29 ± 0.76 mg/g), P. suffruticosa “Taiping Hong” (13.99±1.13 mg/g), and P. suffruticosa “Zhaofen” (13.08±0.85 mg/g). Paeonia ostii “Luoyang Feng Dan” was found to have the lowest content (8.76±0.46 mg/g) of paeonol. In qualitative analysis, 5 tree peony cultivars collected from different plantations in China were used to establish the fingerprint. For the fingerprint analysis, 17 characteristic peaks were used to evaluate similarities among tree peony cultivars, and they were found to show similarities. In short, the results of quantitative and qualitative analyses suggested that there was no significant difference in the chemical composition of Cortex Moutan from different tree peony varieties; however, there were significant differences in the levels of chemical components. The method developed in this study provides an important reference to establish a quality control method for other related traditional Chinese medicinal preparations.

4-Methoxy Sulfonyl Paeonol Inhibits Hepatic Stellate Cell Activation and Liver Fibrosis by Blocking the TGF-β1/Smad, PDGF-BB/MAPK and Akt Signaling Pathways

Liver fibrosis initiates the progression of cirrhosis, and, finally, hepatocellular carcinoma (HCC). The increased proliferation and activation of hepatic stellate cells (HSCs) are crucial for hepatic fibrogenesis. Paeonol is the major vigorous component of Cortex Moutan, a traditional herbal medicine widely used for treating various diseases. Here, we identified a novel paeonol derivative (4-methoxy sulfonyl paeonol, 4-MSP) that inhibits TGF-β1-induced Smad2/3 phosphorylation and collagen expression in HSCs. 4-MSP pretreatment suppressed the PDGF-BB–induced phosphorylation of MAPK pathway members (MEK/ERK, p38, JNK), Akt/p70S6K, and HSC proliferation. However, 4-MSP treatment had no effect on the induction of apoptosis in HSCs. The microarray experiments showed that 4-MSP treatment affects the TGF-β signaling, MAPK cascade, and other pathways related to HSCs activation and proliferation. The administration of 4-MSP to a liver fibrosis mouse model induced by CCl4 significantly decreased the expression of hepatic fibrosis markers (α-SMA, col1A2, TGF-β, and MMP2), and attenuated hepatic collagen deposition and liver damage. In addition, no adverse effects were observed in 4-MSP exposed mice. In conclusion, this novel paeonol-phenylsulfonyl derivative prevents the progression of liver fibrosis through blocking TGF-β1/Smad, PDGF-BB/MAPK, and Akt signaling, which suggests its use as a novel therapeutic against liver fibrosis.

Correction: Pharmacokinetic–pharmacodynamic modeling for Moutan Cortex/Moutan Cortex charcoal and the contributions of the chemical component using support vector regression with particle swarm optimization

Correction for ‘Pharmacokinetic–pharmacodynamic modeling for Moutan Cortex/Moutan Cortex charcoal and the contributions of the chemical component using support vector regression with particle swarm optimization’ by Sixing Pan et al., RSC Adv., 2020, 10, 24454–24462, DOI: 10.1039/D0RA04111D.

Pharmacokinetic–pharmacodynamic modeling for Moutan Cortex/Moutan Cortex charcoal and the contributions of the chemical component using support vector regression with particle swarm optimization

Moutan Cortex (MC) and Moutan Cortex charcoal (MCC) are two kinds of Chinese medicinal materials and effective substances are still unclear. A PK-PD model for MC/MCC is proposed using the support vector regression with particle swarm optimization.